This application requests funds for continuation of a Cell Physiology Training Program that has been developed over the last 15 years with the rebuilding of the Department of Physiology and Biophysics at Case Western Reserve University. The objective of this Training Program is to provide exceptional training of a few, highly qualified and motivated biomedical scientists in the discipline of cellular and molecular physiology and pathophysiology. Cell physiology is broadly defined as the field that is concerned with integration of functions of genes/proteins at the cellular level. Major emphasis is placed on cellular regulatory biology consisting of intracellular signaling, ion transport, and gene regulation. Pre-doctoral trainees and post-doctoral trainees with M.D. degrees are enrolled in graduate Ph.D. programs in either cell physiology, biophysics/bioengineering, or structural biology; post-doctoral trainees complete their training predominantly through guided laboratory research. The Training Faculty of this Program is composed of 17 renowned scientists from 7 different departments of the School of Medicine, with the Department of Physiology and Biophysics as intellectual and administrative center. Cell physiology is the major focus of the Department, which has over 60 active members, including both primary and secondary appointments as the Department has become the center for this discipline in Cleveland. Rigorous pre-doctoral training is provided through graduate programs and includes a set of foundation and advanced courses specifically designed for cell physiology students, laboratory rotations, seminars, journal clubs, and guided research. Progress of trainees is tightly monitored, whereby one of the quality checks consists of the requirement that students publish at least two first-authored articles in the premier, peer-reviewed journal of their respective field. The Program at the time of the renewal provides expanded training opportunities in a wide range of the methodologies that constitute the basic research approaches in the field of cell physiology (chemical and electrical signal transduction, ion and non-electrolyte membrane transport, regulation of gene expression, structure-function relationship of proteins) while at the same time the number of highly qualified applicants has greatly increased.